We have been working on the mitochondrial kinase PINK1, with a particular focus on how loss of function of PINK1 influences mitochondria. Extending previous work, we have shown that absence of PINK1 leads to a number of mitochondrial abnormalities including some evidence of fragmentation, at least in cells in culture. Working on the signaling pathways involved, we have found that cells lacking PINK1 are more sensitive to C2-ceramide, which likely signals through the Akt pathway. Related to this, we have also found that Akt-mediated changes in hexokinase, a mitochondrial protein, control the recruitment of parkin to mitochondria. We plan to further develop this project by examining the role(s) of hexokinase in maintenance of mitochondrial function in the brain.